June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Clinical features of OPA1-related optic neuropathy: a retrospective case series
Author Affiliations & Notes
  • Eric Gaier
    School of Medicine, University of Connecticut Health Center, Farmington, CT
    Neuroscience, University of Connecticut Health Center, Farmington, CT
  • Phillip Skidd
    Neuro-Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Maria Janessian
    Glaucoma, Massachusetts Eye and Ear Infirmary, Boston, MA
    Howe Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Simmons Lessell
    Neuro-Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
    School of Medicine, Harvard Medical School, Boston, MA
  • Dean Cestari
    Neuro-Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
    School of Medicine, Harvard Medical School, Boston, MA
  • Joseph Rizzo
    Neuro-Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
    School of Medicine, Harvard Medical School, Boston, MA
  • Janey Wiggs
    Glaucoma, Massachusetts Eye and Ear Infirmary, Boston, MA
    Howe Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Footnotes
    Commercial Relationships Eric Gaier, None; Phillip Skidd, None; Maria Janessian, None; Simmons Lessell, None; Dean Cestari, None; Joseph Rizzo, Bionic Eye Technology (I), Bionic Eye Technology (P); Janey Wiggs, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1355. doi:
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    • Get Citation

      Eric Gaier, Phillip Skidd, Maria Janessian, Simmons Lessell, Dean Cestari, Joseph Rizzo, Janey Wiggs; Clinical features of OPA1-related optic neuropathy: a retrospective case series. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1355.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Dominant optic atrophy (DOA) is the most common hereditary optic neuropathy. The most common form of DOA, DOA type 1 (Kjer’s disease) accounts for 40-60% of cases and is associated with mutation of the OPA1 gene. Previously, clinical studies focusing on OPA1 mutations have been limited to a few mutations and clinical parameters. In the present study, we evaluated and analyzed detailed clinical information for patients referred to a major tertiary care center for OPA1 testing for suspected DOA.

Methods: In this retrospective case series, we review the clinical records of 62 patients referred for PCR-based sequencing of OPA1. Missense and small deletions/insertions found by sequencing were compared with those reported in the literature, and objective analyses were used to determine the likelihood of pathogenicity for specific DNA changes. A subset of patients was selected for Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The clinical features examined include, but are not limited to, visual acuity, Ishihara testing, automated visual field testing, and dilated fundoscopy.

Results: Clinical data was available for 54 patients (31 male; 23 female). The majority (28/41; 68.3%) were referred by an optometrist/ophthalmologist for a problem related to optic nerve appearance. Of the 62 patients that underwent diagnostic OPA1 sequencing, 18 (29.0%) were found to have potentially disease-causing coding mutations: 3 splice site mutations, 3 missense mutations, and 12 nonsense/truncating mutations. The common TTAG deletion comprised 7 of the 12 nonsense mutations in 4 unrelated families, confirming previous reports of this mutation hot spot. Three sequence mutations are novel. MLPA analysis identified 5 patients with large-scale deletions/duplications unrecognized by sequencing. Deletion spans ranged from 3 exons to the entire gene. Automated visual field testing was the most sensitive measure of disease status as assessed in a subset of individuals followed over 1-5 years.

Conclusions: Our results show that OPA1 mutations are a common cause of optic neuropathy in the tertiary referral setting and large-scale genomic aberrations account for a small subset of OPA1-related neuropathies. Automated visual field testing may be the best measure of disease progression in these patients.

Keywords: 613 neuro-ophthalmology: optic nerve • 463 clinical (human) or epidemiologic studies: prevalence/incidence • 539 genetics  
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